Stein Deborah M, Dutton Richard P, Hess John R, Scalea Thomas M
R Adams Cowley Shock Trauma Centress, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Injury. 2008 Sep;39(9):1054-61. doi: 10.1016/j.injury.2008.03.032. Epub 2008 Jul 25.
Coagulopathy in injured patients is common and is generally treated with fresh frozen plasma (FFP). Response can be variable, thus complete correction may take hours and require large volumes of fluids. High-dose recombinant factor VIIa (FVIIa, Novoseven, Novo Nordisk, Bagsvaerd, Denmark) has been used off-label to treat severe coagulopathy following trauma. Expense has limited use. Recently, we began administering low dose FVIIa (1.2mg) to patients with mild to moderate coagulopathy after trauma, hypothetising that it would be effective and safe.
We retrospectively reviewed consecutive patients who received a low dose of 1.2mg of FVIIa over a 2-year period. Factor VIIa is administered after approval by a gatekeeper at the discretion of the treating physician. Demographics, injury and laboratory data were abstracted as were indications for use, source of coagulopathy, effectiveness, and complications. A two-tailed paired t-test was used to determine significant changes in coagulation parameters and blood product utilisation.
Eighty-one patients received 84 low doses of FVIIa. The mean age of the patients was 51 (+/-22) with a mean ISS of 29 (+/-11). Seventy-three per cent were male and 67% had a traumatic brain injury (TBI) as their primary injury. The aetiology of the coagulopathy in the study population included; TBI (40%), warfarin use (22%), and cirrhosis (13%). Mean prothrombin time (PT) fell from 17.0 s (+/-3.2) to 10.6s (+/-1.4) (p<0.0001). All patients had a good clinical response with no bleeding complications. Utilisation of packed red blood cells and fresh frozen plasma were significantly less in the 24h after FVIIa administration as compared to the 24h prior. Subsequent thromboembolic events were observed in 12 of the 81 patients (15%) and included; cerebrovascular accident (CVA) (6), mesenteric thrombosis (2), myocardial infarction (MI) (1), pulmonary embolism/deep venous thrombosis (PE/DVT) (2), and atrial thrombus (1). Only four of these events were thought to be related to the FVIIa administration, with two of the four contributing to a lethal outcome.
Low dose FVIIa rapidly and effectively treats mild to moderate coagulopathy following injury. This low dose (1.2mg) FVIIa is the smallest available unit dose. It costs approximately the same as 8 units of plasma and may be cost-effective in patients who require high volume factor administration. Low dose FVIIa may be effective in coagulopathic trauma patients who are not in shock but require rapid normalisation of clotting function.
受伤患者的凝血功能障碍很常见，通常用新鲜冰冻血浆（FFP）治疗。反应可能因人而异，因此完全纠正可能需要数小时，且需要大量液体。高剂量重组凝血因子VIIa（FVIIa，诺其，丹麦诺和诺德公司， Bagsvaerd）已被用于治疗创伤后的严重凝血功能障碍，但因费用问题限制了其应用。最近，我们开始对创伤后轻至中度凝血功能障碍患者给予低剂量FVIIa（1.2mg），推测其有效且安全。
我们回顾性分析了连续2年接受1.2mg低剂量FVIIa治疗的患者。FVIIa经主治医生酌情决定，由把关人批准后给药。收集了人口统计学、损伤和实验室数据，以及使用指征、凝血功能障碍的来源、有效性和并发症。采用双尾配对t检验来确定凝血参数和血液制品使用的显著变化。
81例患者接受了84次低剂量FVIIa治疗。患者的平均年龄为51岁（±22岁），平均损伤严重度评分（ISS）为29分（±11分）。73%为男性，67%以创伤性脑损伤（TBI）为主要损伤。研究人群中凝血功能障碍的病因包括：TBI（40%）、华法林使用（22%）和肝硬化（13%）。平均凝血酶原时间（PT）从17.0秒（±3.2秒）降至10.6秒（±1.4秒）（p<0.0001）。所有患者临床反应良好，无出血并发症。与给药前24小时相比，FVIIa给药后24小时内浓缩红细胞和新鲜冰冻血浆的使用量显著减少。81例患者中有12例（15%）发生了随后的血栓栓塞事件，包括：脑血管意外（CVA）（6例）、肠系膜血栓形成（2例）、心肌梗死（MI）（1例）、肺栓塞/深静脉血栓形成（PE/DVT）（2例）和心房血栓（1例）。这些事件中只有4例被认为与FVIIa给药有关，其中4例中有2例导致了致命结局。
低剂量FVIIa能快速有效地治疗创伤后轻至中度凝血功能障碍。这种低剂量（1.2mg）FVIIa是最小可用单位剂量。其成本与8单位血浆大致相同，对于需要大量因子给药的患者可能具有成本效益。低剂量FVIIa可能对非休克但需要快速使凝血功能正常化的凝血功能障碍创伤患者有效。
